During chronic infection or tumour growth antigen-specific T cells acquire an ‘exhausted’ phenotype characterized by expression of multiple inhibitory receptors and down-modulation of effector function. In addition, chronically stimulated T cells also show broad metabolic impairments, which contribute to loss of antigen-specific cells and limited production of effector molecules, such as IFNg. While T cell ‘exhaustion’ is considered to prevent successful immunity, it also protects the organism from excessive immunopathology. We and others have recently shown that CXCR5+TCF1+ memory-like antigen-specific T cells are required to sustain T cell responses under conditions of chronic stimulation. In our recent study, we have further explored the transcriptional base for CD8+ T cell exhaustion. We found that high amounts of transcription factor IRF4 mediate the expression of multiple inhibitory receptors, including PD-1, and the progressive decline in cellular metabolism. Reducing expression of IRF4 allowed for functional and metabolic restoration and promoted the expansion of memory-like antigen-specific T cells required to sustain T cell responses. Thus, we show that IRF4 constitutes a central node in a T cell receptor-responsive transcriptional circuit that sustains the characteristics of exhausted T cells.